Müller glia, or Müller cells, are a type of retinal glial cells, first recognized and described by Heinrich Müller. They are found in the vertebrate retina, which serve as support cells for the neurons of the retina as all glial cells do. They are the most common type of glial cell found in the retina. They span across the entire thickness of the neural retina.
The major function of the Müller cells is to maintain the stability of the retinal extracellular environment by regulation of K+ levels, uptake of neurotransmitters, removal of debris, storage of glycogen, electrical insulation of receptors and other neurons, and mechanical support of the neural retina.
Role in development
Müller glia have been shown to be critical to the development of the retina in mice, serving as promoters of retinal growth and histogenesis via a non-specific esterase mediated mechanism. Müller glia have also been implicated to serve as guidepost cells for the developing axons of neurons in the chick retina. Studies using a zebrafish model of Usher syndrome have implicated a role for Müller glia in synaptogenesis, the formation of synapses.
As glial cells, Müller glia serve a secondary but important role to neurons. As such, Müller glia have been shown to serve as important mediators of neurotransmitter (acetylcholine and GABA specifically) degradation and maintenance of a favorable retinal microenvironment in turtles. Müller glia have also been shown to be important in the induction of the enzyme glutamine synthetase in chicken embryos, which is an important actor in the regulation of glutamine and ammonia concentrations in the central nervous system. Müller glia have been further identified as fundamental to the transmission of light through the vertebrate retina due to their unique funnel shape, orientation within the retina and more favorable physical properties.
Use in research
Müller glia are currently being studied for their role in neural regeneration, a phenomenon that is not known to occur in humans. Studies to this end of Müller glia in both the zebrafish and chicken retina have been performed, with the exact molecular mechanism of regeneration remaining unclear. Further studies performed in mice have shown that Müller glia begin to dedifferentiate and exhibit cell cycle markers, yet do not complete mitosis, which implies there is a block of the regeneration process that is unique to mammals. Studies in human models have demonstrated that Müller glia have the potential to serve as stem cells in the adult retina and are efficient rod photoreceptor progenitors.
Following injury to the retina, it has been shown in zebrafish that Müller glia undergo dedifferentiation into multipotent progenitor cells. The progenitor cell can then divide and differentiate into a number of retinal cell types, including photoreceptor cells, that may have been damaged during injury. Additionally, further research has shown that Müller glia act as light collectors in the mammalian eye, analogous to the fiber optic plate, funneling light to the rod and cone photoreceptors.
- Bhattacharjee, J.; Sanyal, S. (1975). "Developmental origin and early differentiation of retinal Müller cells in mice". Journal of Anatomy 120 (Pt 2): 367–372. PMC 1231976. PMID 1201967.
- Meller, K.; Tetzlaff, W. (1976). "Scanning electron microscopic studies on the development of the chick retina". Cell and tissue research 170 (2): 145–159. doi:10.1007/bf00224296. PMID 954051.
- Phillips, J. B.; Blanco-Sanchez, B.; Lentz, J. J.; Tallafuss, A.; Khanobdee, K.; Sampath, S.; Jacobs, Z. G.; Han, P. F.; Mishra, M.; Titus, T. A.; Williams, D. S.; Keats, B. J.; Washbourne, P.; Westerfield, M. (2011). "Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function". Disease Models & Mechanisms 4 (6): 786–800. doi:10.1242/dmm.006429. PMC 3209648. PMID 21757509.
- Sarthy, P. V.; Lam, D. M. (1978). "Biochemical studies of isolated glial (muller) cells from the turtle retina". The Journal of Cell Biology 78 (3): 675–684. doi:10.1083/jcb.78.3.675. PMC 2110200. PMID 29902.
- Linser, P.; Moscona, A. A. (1979). "Induction of glutamine synthetase in embryonic neural retina: localization in Müller fibers and dependence on cell interactions". Proceedings of the National Academy of Sciences of the United States of America 76 (12): 6476–6480. doi:10.1073/pnas.76.12.6476. PMC 411888. PMID 42916.
- Franze, K.; Grosche, J.; Skatchkov, S. N.; Schinkinger, S.; Foja, C.; Schild, D.; Uckermann, O.; Travis, K.; Reichenbach, A.; Guck, J. (2007). "Müller cells are living optical fibers in the vertebrate retina". Proceedings of the National Academy of Sciences 104 (20): 8287–8292. doi:10.1073/pnas.0611180104. PMC 1895942. PMID 17485670.
- WebVision: Regeneration in the Visual System of Adult Mammals
- Fausett, BV; Goldman, D (2006). "A role for a1 tubulin-expressing Müller glia in regeneration of the injured zebrafish retina". J. Neurosci 26: 6303–6313. doi:10.1523/jneurosci.0332-06.2006.
- Raymond, PA; et al. (2006). "Molecular characterization of retinal stem cells and their niches in adult zebrafish". BMC Dev Biol. 6: 36.
- Fischer, AJ (2001). "Müller glia are a potential source of neural regeneration in the postnatal chicken retina". Nat Neurosci 4: 247–52.
- Joly, S.; Pernet, V.; Samardzija, M.; Grimm, C. (2011). "Pax6-positive müller glia cells express cell cycle markers but do not proliferate after photoreceptor injury in the mouse retina". Glia 59 (7): 1033–1046. doi:10.1002/glia.21174. PMID 21500284.
- Bhatia, B.; Jayaram, H.; Singhal, S.; Jones, M. F.; Limb, G. A. (2011). "Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye". Experimental Eye Research 93 (6): 852–861. doi:10.1016/j.exer.2011.09.015. PMC 3268355. PMID 21989110.
- Giannelli, S. G.; Demontis, G. C.; Pertile, G.; Rama, P.; Broccoli, V. (2011). "Adult Human Müller Glia Cells Are a Highly Efficient Source of Rod Photoreceptors". Stem Cells 29 (2): 344–356. doi:10.1002/stem.579. PMID 21732491.
- Bernardos RL, Barthel LK, Meyers JR, Raymond PA. Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. J Neurosci. 2007 Jun 27;27(26):7028-40. PMID 17596452
- Müller cells acting as light conductor at The Register, based on Franze et al., Müller cells are living optical fibers in the vertebrate retina, PNAS 104(20):8287–8292, 15 May 2007 | 10.1073/pnas.0611180104
|Wikimedia Commons has media related to Müller cells.|
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- Reichenbach A, Faude F, Enzmann V, et al. (1997). "The Müller (glial) cell in normal and diseased retina: a case for single-cell electrophysiology". Ophthalmic Res. 29 (5): 326–40. doi:10.1159/000268031. PMID 9323724.
- NIF Search - Muller Cell via the Neuroscience Information Framework